Heart failure (HF) is a major health concern, which accounts for 1–2% of all hospital admissions. Nevertheless, there remains a knowledge gap concerning which interventions contribute to effective ...prevention of HF (re)hospitalization. Therefore, this umbrella review aims to systematically review meta-analyses that examined the effectiveness of interventions in reducing HF-related (re)hospitalization in HFrEF patients. An electronic literature search was performed in PubMed, Web of Science, PsycInfo, Cochrane Reviews, CINAHL, and Medline to identify eligible studies published in the English language in the past 10 years. Primarily, to synthesize the meta-analyzed data, a best-evidence synthesis was used in which meta-analyses were classified based on level of validity. Secondarily, all unique RCTS were extracted from the meta-analyses and examined. A total of 44 meta-analyses were included which encompassed 186 unique RCTs. Strong or moderate evidence suggested that catheter ablation, cardiac resynchronization therapy, cardiac rehabilitation, telemonitoring, and RAAS inhibitors could reduce (re)hospitalization. Additionally, limited evidence suggested that multidisciplinary clinic or self-management promotion programs, beta-blockers, statins, and mitral valve therapy could reduce HF hospitalization. No, or conflicting evidence was found for the effects of cell therapy or anticoagulation. This umbrella review highlights different levels of evidence regarding the effectiveness of several interventions in reducing HF-related (re)hospitalization in HFrEF patients. It could guide future guideline development in optimizing care pathways for heart failure patients.
Summary
Immune checkpoint blockade has resulted in durable responses in patients with metastatic melanoma, but only in a fraction of treated patients. For immune checkpoint inhibitors (ICI) to be ...effective, sufficient infiltration with tumor‐reactive T cells is essential. Oncolytic viruses (OV) selectively replicate in and lyse tumor cells and so induce an immunogenic form of cell death, providing at once a source of tumor‐associated (neo)antigens and of danger signals that together induce effective T cell immunity and tumor infiltration. Melanoma‐associated suppression of dendritic cell (DC) differentiation effectively hampers OV‐ or immune checkpoint inhibitor (ICI)‐induced anti‐tumor immunity, due to a consequent inability to prime and attract anti‐tumor effector T cells. Here, we set out to study the effect of ORCA‐010, a clinical stage oncolytic adenovirus, on DC differentiation and functionality in the context of human melanoma. In melanoma and monocyte co‐cultures, employing a panel of five melanoma cell lines with varying origins and oncogenic mutation status, we observed clear suppression of DC development with apparent skewing of monocyte differentiation to a more M2‐macrophage‐like state. We established the ability of ORCA‐010 to productively infect and lyse the melanoma cells. Moreover, although ORCA‐010 was unable to restore DC differentiation, it induced activation and an increased co‐stimulatory capacity of monocyte‐derived antigen‐presenting cells. Their subsequent ability to prime effector T cells with a type I cytokine profile was significantly increased in an allogeneic mixed leukocyte reaction. Our findings suggest that ORCA‐010 is a valuable immunotherapeutic agent for melanoma.
The current study examined the effect of supplementing lambs with algae. Forty, three month old lambs were allocated to receive a control ration based on oats and lupins (n=20) or the control ration ...with DHA-Gold™ algae (~2% of the ration, n=20). These lambs came from dams previously fed a ration based on either silage (high in omega-3) or oats and cottonseed meal (OCSM: high in omega-6) at joining (dam nutrition, DN). Lamb performance, carcase weight and GR fat content were not affected by treatment diet (control vs algae) or DN (silage vs OSCM). Health claimable omega-3 fatty acids (EPA+DHA) were significantly greater in the LL of lambs fed algae (125±6mg/100g meat) compared to those not fed algae (43±6mg/100g meat) and this effect was mediated by DN. Supplementing with algae high in DHA provides a means of improving an aspect of the health status of lamb meat.
•A DHA rich algae diet had no impact on growth, or carcase fatness of lambs.•DHA in the m. longissimus was significantly increased due to algae feeding.•Feeding DHA rich algae increased lipid oxidation.•Feeding DHA rich algae did not impact on meat colour stability.
The objective of the present study was to examine the factors associated with the death of neonatal lambs. Postmortem autopsy data were collected from 3198 newborn lambs in the Sheep CRCs Information ...Nucleus Flock situated in various environments throughout southern Australia. The proportion dying by category from highest to lowest was starvation–mismothering (25%), stillbirth (21%), birth injury (18%), dystocia (9%), death in utero–prematurity (10%), predation (7%), cold exposure (5%), undiagnosed (4%), infection (1%) or misadventure (1%). Factors best explaining the probability of lambs falling into a death category included both birth type and birthweight for dystocia, stillbirth, starvation–mismothering and death in utero–prematurity. The probability of a lamb falling into any category was predicted at the mean birthweight, within birth type. Single-born lambs were more likely to die from dystocia and stillbirth, while twin lambs were more likely to die from birth injury, starvation–mismothering or from undiagnosed causes. Triplet lambs were more likely to die from starvation–mismothering or death in utero–prematurity. Sire type (Merino, maternal or terminal) did not affect the proportions of lambs within any category. The proportions lost to each cause of death were largely consistent among locations, despite the rate of death varying. Dystocia, stillbirth and birth injury, as evidenced by the presence of oedema around the head and neck or by lesions of the central nervous system, accounted for 48% of autopsied lambs. We conclude that for improvements to occur in the rates of lamb survival, the Australian sheep industry must focus on minimising losses due to dystocia, stillbirth, birth injury and starvation.
Given the lack of data that relates consumer acceptance of lamb colour to instrument measures a study was undertaken to establish the acceptability thresholds for fresh and displayed meat. Consumers ...(
n
=
541) were asked to score 20 samples of lamb loin (
m.
longissimus thoracis et lumborum; LL) on an ordinal scale of 1 (very acceptable) to 5 (very unacceptable). A sample was considered acceptable by a consumer if it scored three or less. Ten samples were used for testing consumer response to fresh colour and 10 to test consumer response to colour during display of up to 4
days. The colour of fresh meat was measured using a Minolta chromameter with a closed cone and a Hunter Lab Miniscan was used for measuring meat on display. For fresh meat when the
a
∗ (redness) and
L
∗ (lightness) values are equal to or exceed 9.5 and 34, respectively, on average consumers will consider the meat colour acceptable. However
a
∗ and
L
∗ values must be much higher (14.5 and 44, respectively) to have 95% confidence that a randomly selected consumer will consider a sample acceptable. For aged meat, when the wavelength ratio (630/580
nm) and the
a
∗ values are equal to or greater than 3.3 and 14.8, respectively, on average consumers will consider the meat acceptable. These thresholds need to be increased to 6.8 for ratio (630/580
nm) and 21.7 for
a
∗ to be 95% confident that a randomly selected consumer will consider a sample acceptable.
Loss of cellular adhesion leads to the progression of breast cancer through acquisition of anchorage independence, also known as resistance to anoikis. Although inactivation of E-cadherin is ...essential for acquisition of anoikis resistance, it has remained unclear how metastatic breast cancer cells counterbalance the induction of apoptosis without E-cadherin-dependent cellular adhesion. We report here that E-cadherin inactivation in breast cancer cells induces PI3K/AKT-dependent FOXO3 inhibition and identify FOXO3 as a novel and direct transcriptional activator of the pro-apoptotic protein BMF. As a result, E-cadherin-negative breast fail to upregulate BMF upon transfer to anchorage independence, leading to anoikis resistance. Conversely, expression of BMF in E-cadherin-negative metastatic breast cancer cells is sufficient to inhibit tumour growth and dissemination in mice. In conclusion, we have identified repression of BMF as a major cue that underpins anoikis resistance and tumour dissemination in E-cadherin-deficient metastatic breast cancer.
The Warner–Bratzler shear force (WBSF) of 335 lamb m. longissimus lumborum (LL) caudal and cranial ends was measured to examine and simulate the effect of replicate number (r: 1–8) on the precision ...of mean WBSF estimates and to compare LL caudal and cranial end WBSF means. All LL were sourced from two experimental flocks as part of the Information Nucleus slaughter programme (CRC for Sheep Industry Innovation) and analysed using a Lloyd Texture analyser with a Warner–Bratzler blade attachment. WBSF data were natural logarithm (ln) transformed before statistical analysis. Mean ln(WBSF) precision improved as r increased; however the practical implications support an r equal to 6, as precision improves only marginally with additional replicates. Increasing LL sample replication results in better ln(WBSF) precision compared with increasing r, provided that sample replicates are removed from the same LL end. Cranial end mean WBSF was 11.2±1.3% higher than the caudal end.
•Warner–Bratzler shear force result precision improves as replicate number increases.•Only minor precision improvements were found when replicate number exceeded six.•Cranial loin ends had higher Warner–Bratzler shear force than caudal ends.
This study investigated the effects of using medium voltage (~300V) electrical stimulation (ES) and ageing on alpaca meat. A total of 50 huacaya alpacas were distributed across three age groups (18, ...24 and 36months) and two genders (females and castrated males). At 24h post mortem the m. longissimus thoracis et lumborum (LL) and m. semimembranosus (SM) muscles were removed and aged for either 5 or 10days. In comparison to non-ES samples, ES significantly reduced: LL purge values by 3.0% and LL shear force (SF) at 5 and 10days (by 21.6N and ageing further reduced tenderness by 6.6N), and SM SF by 5.8N with significant age effects observed in both ES and non-ES SM samples, such that SF increased by 0.53N with each month increase in animal age. Consumers rated ES samples higher on tenderness, juiciness, flavour and overall rating. ES and ageing of alpaca carcasses are recommended.
•Electrical stimulation should be used to minimise cold shortening occurring in alpaca carcasses.•Electrical stimulation and ageing alpaca meat improve shear force values.•Electrically stimulated product was rated higher on all levels of consumer sensory evaluation.•Alpaca meat has its own unique colour characteristics and meat quality parameters.
An experiment was undertaken to examine the effect of rapid pH fall at a high muscle temperature on meat and eating quality of two beef cuts (striploin and cube roll). From 115 beef steer carcasses ...of which the right side of each carcass was subjected to electrical stimulation, 25 carcasses which exhibited the largest difference in the rate of pH fall in the M. longissimus between sides were selected for subsequent sampling. All of the stimulated sides missed the ‘ideal’ pH/temperature window (defined as temperature at pH 6 in the M. longissimus <35°C and >12°C) at the upper end, as did several of the non-stimulated sides. The mean temperature at pH 6 for stimulated sides from modelling was 40.9 versus 33.3°C for non-stimulated sides. Despite the significant effect of stimulation on pH decline there was no statistically significant impact on shear force or sensory traits of the M. longissimus, but there was a significant effect of aging on these traits. There was no effect of stimulation or pH decline on drip loss of the striploin. After 14 days of aging there was no effect of stimulation or ultimate pH on striploin purge, but there was a significant effect of pH decline. This was not, however, evident for purge of the cube roll aged for either 4 or 42 days. The redness of the cube rolls as reflected by a* values declined with days of display, with the decline more rapid for samples aged for 42 days compared with those aged for 4 days. For meat aged and displayed identically, the a* values were on average significantly lower for meat from non-stimulated carcasses, but apart from aging there was no effect on the wavelength ratio 630/580 nm, an indicator of the formation of metmyoglobin. There was also evidence that a rapid decline in pH increased the onset of lipid oxidation.
This study investigated the effects of feeding a mixed grain supplement and tenderstretching (TS) alpaca carcasses on meat quality. A total of 56 castrated 24month old alpacas were divided into two ...treatments (pasture-only, and pasture plus supplementation). Supplemented groups were fed a mixed grain ration in addition to ad lib pasture for 10weeks. Animals were slaughtered across two kill days (n=28). One half of each carcass was suspended by the pelvis (TS) prior to chilling, and the other half was Achilles tendon hung (AH). After 24h, muscles were removed and aged for 10 and 25d. TS significantly increased sarcomere length and reduced shear force and cooking loss in the m. semimembranosus. This trend was not observed in other muscles including the m. longissimus thoracis et lumborum (LL) and m. psoas major. Ageing period resulted in a marginal improvement in LL tenderness. There is clear evidence that TS improves tenderness in the hindquarter of alpacas.
•Tenderstretching improved shear force values in the m. semimembranosus (SM)•Tenderstretching elongated sarcomeres and reduced cooking loss in the SM•Tenderstretching reduced sarcomere length in the m. psoas major•Tenderstretching and ageing had minimal effect on the LL muscle•Mixed grain supplementation had minimal impact upon alpaca meat quality traits